van der Zee A G, Hollema H, Suurmeijer A J, Krans M, Sluiter W J, Willemse P H, Aalders J G, de Vries E G
Department of Gynecology, University Hospital Groningen, The Netherlands.
J Clin Oncol. 1995 Jan;13(1):70-8. doi: 10.1200/JCO.1995.13.1.70.
To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma.
Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival.
P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately.
Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.
确定P-糖蛋白（P-gp）、谷胱甘肽S-转移酶（GST）π、c-erbB-2和p53免疫染色在晚期卵巢癌患者中的预后价值。
对89例原发性肿瘤以及38例含铂和阿霉素化疗的晚期卵巢癌患者化疗后的残留肿瘤（P-gp和GST π）进行P-gp、GST π、c-erbB-2和p53免疫染色。免疫染色结果与临床病理预后因素、化疗反应、无进展生存期（PFS）和总生存期相关。
P-gp和GST π免疫反应性分别见于13例（15%）和79例（89%），与任何其他预后因素、PFS或总生存期均无关联。c-erbB-2免疫反应性见于18例（20%），与未分化组织类型相关（P <.05），但与PFS或总生存期无关。p53免疫反应性见于31例（35%）的细胞核和9例（10%）的细胞质。细胞核p53染色与III级肿瘤、腹水超过1 L以及首次剖腹手术后残留肿瘤超过2 cm相关。细胞核p53染色与较短的PFS（相对危险度[RR]，3.3；95%可信区间[CI]，2.0至5.6）和总生存期（RR，2.6；95% CI，1.7至3.8）相关。在对腹水超过1 L或年龄超过50岁进行校正后，细胞核p53染色在III/IV期肿瘤中不具有独立的预后意义。化疗后残留肿瘤中P-gp染色的频率（38例中的18例）高于未治疗肿瘤（89例中的13例）（P <.001）。没有任何预后参数组合能够充分预测化疗反应。
卵巢癌中p53的细胞核免疫反应性与较短的PFS和总生存期以及更具侵袭性的肿瘤生长决定因素相关。化疗后残留肿瘤中P-gp免疫反应性的较高频率表明含阿霉素的联合化疗可诱导卵巢癌中的P-gp。对P-gp、GST π、c-erbB-2和p53的检测不能更充分地预测化疗反应。
